Young children with Down syndrome show normal development of circadian rhythms, but poor sleep efficiency: a cross-sectional study across the first 60 months of life

Abstract

Objectives: To evaluate sleep consolidation and circadian activity rhythms in infants and toddlers with Down syndrome (DS) under light and socially entrained conditions within a familiar setting. Given previous human and animal data suggesting intact circadian regulation of melatonin across the day and night, it was hypothesized that behavioral indices of circadian rhythmicity would likewise be intact in the sample with DS.

Methods: A cross-sectional study of 66 infants and young children with DS, aged 5-67 months, and 43 typically developing age-matched controls. Sleep and measures of circadian robustness or timing were quantified using continuous in-home actigraphy recordings performed over seven days. Circadian robustness was quantified via time series analysis of rest-activity patterns. Phase markers of circadian timing were calculated alongside these values. Sleep efficiency was also estimated based on the actigraphy recordings.

Results: This study provided further evidence that general sleep quality is poor in infants and toddlers with DS, a population that has sleep apnea prevalence as high as 50% during the preschool years. Despite poor sleep quality, circadian rhythm and phase were preserved in children with DS and displayed similar developmental trajectories in cross-sectional comparisons with a typically developing (TD) cohort. In line with past work, lower sleep efficiency scores were quantified in the group with DS relative to TD children. Infants born with DS exhibited the worst sleep fragmentation; however, in both groups, sleep efficiency and consolidation increased across age. Three circadian phase markers showed that 35% of the recruitment sample with DS was phase-advanced to an earlier morning schedule, suggesting significant within-group variability in the timing of their daily activity rhythms.

Conclusions: Circadian rhythms of wake and sleep are robust in children born with DS. The present results suggest that sleep fragmentation and any resultant cognitive deficits are likely not confounded by corresponding deficits in circadian rhythms.

Keywords: Actigraphy; Circadian rhythms; Development; Down syndrome; NPCRA (Non-Parametric Circadian Rhythm Analyses); Sleep.

Fig. 1

A and B. The Down syndrome (DS) and typically developing (TD) groups were equivalent along several demographic and social background factors, and exhibited a similar age distribution. Categories listed under sleep characteristics were curated from questions on the Children's Sleep Habits Questionnaire. Based on these questions, children from the DS sample were found to co-sleep less with parents or siblings during nighttime rest than those from the TD sample. Nearly all the children in the survey (>90%), irrespective of genetic background, were classified as habitual nappers. (C) Map of the recruitment area. States in black mark where the participants lived at the time of the actigraphy recordings. (D) Heat map of a minute-by-minute activity profile generated from several days of recording from a 2.5-year-old male toddler with DS. Lack of color diffusion in the onset and offset areas suggests that the movement of this individual was confined to two blocks of activity occurring at approximately the same time each day, separated by a routine nap. (E) High-resolution actogram showing the absolute activity or inactivity of a 2-year-old female toddler with DS. Data are vertically aligned; such that one 24-h day of movement is shown per line, with successive days appearing one below the other. Any movement registered with the Actiwatch, no matter the intensity, was tallied with a black tick. White space indicates complete inactivity. The graph suggests that the child had robust circadian patterns of behavior.

Fig. 2

A–D. Quantitative assessment of circadian robustness in the Down syndrome (DS) (green squares) and typically developing (TD) (purple circles) groups under entrained conditions. Raw values for LSP_24h, FFT_24h, IV, and IS are plotted for each study participant as a function of age. The goodness-of-fit (R² linear) and slope of the regression lines fitted to each panel suggest that circadian rhythms of behavioral activity mature equally well in children with and without DS from 6 months to 5 years. PN, dominant frequency in the Lomb-Scargle periodogram; FFT, fast Fourier transform; NPCRA, Non-parametric circadian rhythm analysis; IV, Intradaily variability; IS, Interdaily stability; AU, arbitrary units. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

A and B. Raw NPCRA-RA values, and raw values for the RA components M10 and L5, are plotted for each study participant as a function of age (TD RA = purple circles; TD M10 = purple circles; TD L5 = upside down triangles; DS RA = green squares; DS M10 = green squares; DS L5 = green diamonds). The goodness-of-fit and slope of the regression lines fitted to the RA scatter plot suggest that RA increases at a similar rate in both the Down syndrome (DS) and typically developing (TD) groups. However, children with DS have smaller RAs compared with children without DS matched for developmental time point. B and C. RA reductions in the Down syndrome (DS) group appear to result from differences in L5, but not M10. M10 and L5 values change in a similar fashion across age in both groups, but L5 values are up-shifted in infants, toddlers, and school-aged children with DS compared with their typically developing (TD) peers. D and E. Raw values for sleep efficiency and duration are plotted for each study participant as a function of age (typically developing (TD) = orange circles; Down syndrome (DS) = green squares). Sleep is better consolidated over the course of development in both the DS and TD groups, but its efficiency is significantly lower in children with DS. Sleep duration does not change from 6 months to 5 years, but is also lower in the DS group by a small, but significant, margin. NPCRA, Non-parametric circadian rhythm analysis; RA, relative amplitude; M10, Most active 10-h period of the day; L5, Least active 5-h period of the day. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

A. Bar graph showing the variation exhibited in an individual's phase marker timing averaged within the Down syndrome (DS) and typically developing (TD) groups (onset = the time of day when person awakes; acrophase = time of day when person is most physically active; offset = time of day when person falls asleep; SD = standard deviation). Relative to the TD sample, young children with DS exhibit no evidence of circadian dispersion in the times of day when they wake-up, are most highly active, or fall asleep. In both groups, the schedule of these events deviated by 30–60 min from one day to the next during the actigraphy recording period. B and C. The average onset (lower left panel), acrophase (lower middle panel), and offset (lower right panel) times displayed by each study participant is plotted against age. These phase markers do not change appreciably over the course of development, but are more widely distributed in children with Down syndrome (DS) compared with typically developing (TD) controls. In particular, more children with DS than TD have exaggerated chronotypes, where their activity is biased towards either earlier-than-average parts of the day (ie, larks; extreme-morning people) or later-than-average parts of the day (ie, owls; evening-type people) (TD = purple circles and bar graphs; DS = green squares and bar graphs). Heat map inserts provide an alternative visualization to this chronotype spread; the divergence from the sample mean of each study participant's average “stable” onset, acrophase, and offset time is color coded so that red lines indicate subjects with phase marker values further away from the group average. DS heat maps appear more in red than TD ones. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

The average onset, acrophase, and offset times calculated for each subject in the Down syndrome (DS) (green squares) and typically developing (TD) (red circles) groups are plotted along the x-axis and organized according to their intra-individual day-to-day variation (y-axis). These data suggest that the DS “lark” chronotype subgroup (indicated by arrows in the lower left of the morning, afternoon, and evening cluster of data points) is particularly stable relative to other chronotypes observed in TD children or those with DS. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)